Interrelationships Between Oxidative Stress, Cytokines, and Psychotic Symptoms and Executive Functions in Patients With Chronic Schizophrenia

Objective Accumulating evidence has demonstrated that the pathophysiology of schizophrenia is involved in various abnormalities in oxidative stress markers and cytokines closely related to synaptic plasticity. However, the interactive effects among key cytokines, oxidative stress, and executive dysfunction and symptoms of schizophrenia have not been investigated yet. Methods A total of 189 patients with chronic schizophrenia and 60 controls were recruited in the current study. Tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-8, IL-6, and IL-2 levels; catalase, glutathione peroxidase, and superoxide dismutase (SOD) activities; and malondialdehyde (MDA) levels were determined in patients and controls. Executive function was evaluated by the Wisconsin card sorting tests, the verbal fluency tests, and the Stroop word-color test. Clinical symptoms were evaluated by the Positive and Negative Syndrome Scale. Results Relative to the controls, the patients had lower activities of SOD and glutathione peroxidase and levels of TNF-alpha, but higher levels of MDA, IL-8, IL-6, and IL-2 (all p values < .05). A significant negative relationship between SOD activity and IL-8 levels was found only in patients (beta = -0.44, p = .008). Furthermore, we found that an interactive effect of low TNF-alpha level and high MDA level was associated with negative symptoms (beta = -0.02, p = .01). Moreover, the interactive effects of IL-8 and MDA or IL-8 and SOD were correlated with executive function only in patients (beta = 0.23, p = .02; beta = 0.09, p = .03). Conclusions Our findings suggest that the interrelationships between oxidative stress markers and cytokines occur in schizophrenia patients, which may be the basis of their pathological mechanisms underlying clinical symptoms and cognitive dysfunction.